On 2 October 2018, Jeff P. Sharman from the Willamette Valley Cancer Institute and Research Center, Oregon, USA and colleagues, published in Leukemia & Lymphoma the final analysis of the phase II trial GATHER (NCT01414855). In this open-label, multicenter study, the efficacy and safety of obinutuzumab (RO5072759 [GA101]) in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) chemotherapy in patients with advanced diffuse large B-cell lymphoma (DLBCL) was evaluated.

DLBCL is one of the most common lymphomas and with the current standard of care (rituximab and CHOP), approximately 60% of patients are cured or improve. Nevertheless, there is still 40% of patients who remain uncured. Obinutuzumab is a glycoengineered, humanized, type 2 anti-CD20 monoclonal antibody with high anti-tumor activity. In this phase II trial, the safety and efficacy of obinutuzumab in combination with CHOP (G-CHOP) was investigated, with a minimum of three years follow-up, in newly-diagnosed advanced DLBCL patients. The primary outcomes of the study were overall response rate (ORR) and complete response (CR) rates calculated by investigator assessment, while secondary outcomes included independent review of ORR and CR, as well as progression-free survival (PFS) and overall survival (OS). The importance of the cell of origin (COO) on the efficacy and safety of a shorter duration infusion of obinutuzumab was also evaluated in this study.

Patients received eight 21-day cycles (10 doses) of 1000 mg obinutuzumab intravenously (IV) on Day 1 of cycles 1–8 with additional doses on Day 8 and Day 15 of cycle 1, in combination with six cycles of standard CHOP (C: 750 mg/m2 IV Day 1; H: 50 mg/m2 IV Day 1; O: 1.4 mg/m2 that could be capped at 2 mg IV Day 1; and P: 100 mg orally Days 1–5)

For prophylaxis against infusion-related reactions (IRR), acetaminophen 650−1000 mg and antihistamines e.g. diphenhydramine 50−100 mg) were administered orally 30 to 60 min before each obinutuzumab infusion. The use of prophylactic corticosteroids was considered for high-risk IRR patients (administered in n = 71 patients)

For neutropenia prophylaxis, granulocyte-colony stimulating factor (filgrastim) was administered to patients ≥ 60 years old or with comorbidities and was strongly recommended for all patients in cycle 1 based on the incidence of neutropenia in previous studies

Primary analysis cut-off date was April 2013, while the final analysis cut-off date was December 2016 with a data snapshot date of March 2017

Key findings

Investigator-assessed ORR and CR rate were 82.0% and 55.0%, respectively. Independently reviewed ORR and CR rate were similar at 75.0% and 58.0%, respectively

At final analysis, median observation time for time-to-event endpoints was 50.7 months (range, 3.5–63.2 months)

Investigator-assessed PFS values were not affected by IPI:

Median PFS was 48.3 months (95% CI, 46.1–58.2)

First-year PFS was 84.2% (95% CI, 76.9–91.6)

Two-year PFS was 76.3% (95% CI, 67.7–85.0)

Three-year PFS was 71.6% (95% CI, 62.3–80.9)

Independent review PFS values were similar to the ones from the investigator assessment:

The phase II GATHER trial demonstrated that G-CHOP is a safe first-line treatment with good efficacy for patients with advanced DLBCL. The authors stated that despite the fact that initial obinutuzumab administration was frequently associated with IRRs, following the first infusion IRRs were uncommon, mild and manageable.

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